LIPOSOME-ENCAPSULATED MURAMYL TRIPEPTIDE UP-REGULATES MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR GENE-EXPRESSION IN HUMAN MONOCYTES AT THE TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a novel immune modulator that is now under investigation against metastatic melanoma and osteosarcoma. We have already reported that L-MTP-PE induced monocyte-mediated tumoricidal activity and up-regulation of the tumor necrosis factor and interleukin-1 (IL-1) in vivo and in vitro. We now demonstrate that L-MTP-PE also induces monocyte chemotactic and activating factor (MCAF) mRNA expression at both the transcriptional and post-transcriptional levels. Monocyte chemotactic activity was also present in the supernatants of L-MTP-PE-stimulated cells. In monocytes, the increased expression of MCAF was induced rapidly (by 2 h) but was short-lived. By 4 h, MCAF mRNA had decreased to background level. We found no change in MCAF mRNA levels in lymphocytes exposed to L-MTP-PE. We therefore conclude that L-MTP-PE selectively up-regulates MCAF expression in monocytes and that MCAF may play a role in the tumoricidal and immune-stimulating activity of L-MTP-PE.